Journal of Applied Physiology AJP: Advances in Physiology Education
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J Appl Physiol 91: 1152-1159, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 3, 1152-1159, September 2001

Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation

Marina Puig-De-Morales1, Mireia Grabulosa1, Jordi Alcaraz1, Joaquim Mullol2, Geoffrey N. Maksym3, Jeffrey J. Fredberg4, and Daniel Navajas1

1 Unitat Biofísica i Bioenginyeria, Facultat Medicina, Universitat Barcelona-IDIBAPS and 2 Hospital Clínic, 08036 Barcelona, Spain; 3 School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5; and 4 Harvard School of Public Health, Boston, Massachusetts 02115

Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Science 260: 1124-1127, 1993) is a useful technique for probing cell micromechanics. The technique is based on twisting ligand-coated magnetic microbeads bound to membrane receptors and measuring the resulting bead rotation with a magnetometer. Owing to the low signal-to-noise ratio, however, the magnetic signal must be modulated, which is accomplished by spinning the sample at ~10 Hz. Present demodulation approaches limit the MTC range to frequencies <0.5 Hz. We propose a novel demodulation algorithm to expand the frequency range of MTC measurements to higher frequencies. The algorithm is based on coherent demodulation in the frequency domain, and its frequency range is limited only by the dynamic response of the magnetometer. Using the new algorithm, we measured the complex modulus of elasticity (G*) of cultured human bronchial epithelial cells (BEAS-2B) from 0.03 to 16 Hz. Cells were cultured in supplemented RPMI medium, and ferromagnetic beads (~5 µm) coated with an RGD peptide were bound to the cell membrane. Both the storage (G', real part of G*) and loss (G", imaginary part of G*) moduli increased with frequency as omega alpha (2pi  × frequency) with alpha  approx  1/4. The ratio G"/G' was ~0.5 and varied little with frequency. Thus the cells exhibited a predominantly elastic behavior with a weak power law of frequency and a nearly constant proportion of elastic vs. frictional stresses, implying that the mechanical behavior conformed to the so-called structural damping (or constant-phase) law (Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ, LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619-1632, 2000). We conclude that frequency domain demodulation dramatically increases the frequency range that can be probed with MTC and reveals that the mechanics of these cells conforms to constant-phase behavior over a range of frequencies approaching three decades.

cell mechanics; cell viscoelasticity; complex elastic modulus; power law rheology; structural damping; magnetic tweezers


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